Cancer treatment reviews
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Cancer treatment reviews · Jun 2006
ReviewInactivation of O6-alkylguanine DNA alkyltransferase as a means to enhance chemotherapy.
DNA adducts at the O6-position of guanine are a result of the carcinogenic, mutagenic and cytotoxic actions of methylating and chloroethylating agents. The presence of the DNA repair protein O6-alkylguanine-DNA alkyltransferase (AGT) renders cells resistant to the biological effects induced by agents that attack at this position. O6-Benzylguanine (O6-BG) is a low molecular weight substrate of AGT and therefore, results in sensitizing cells and tumors to alkylating agent-induced cytotoxicity and antitumor activity. ⋯ O6-BG has also been found to enhance the cytotoxicity of agents that do not form adducts at the O6-position of DNA, including platinating agents. O6-BG's mechanism of action with these agents is not fully understood; however, it is independent of AGT activity or AGT inactivation. A better understanding of the effects of this agent will contribute to its clinical usefulness and the design of better analogs to further improve cancer chemotherapy.
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Cancer treatment reviews · Jun 2006
Review Meta AnalysisOpioid switching: a systematic and critical review.
Cancer patients with pain may not respond to increasing doses of opioids because they develop adverse effects before achieving an acceptable analgesia, or the analgesic response is poor, despite a rapid dose escalation. Opioid switching may significantly improve the balance between analgesia and adverse effects. We conducted a systematic review of existing literature on opioid switching. ⋯ Reasons for switching may influence the dose of the alternative drug. Opioid conversion should not be a mere mathematical calculation, but just a part of a more comprehensive evaluation of pain, adverse effect intensity, comorbidities, and concomitant drugs. The process of reaching an optimal dose should be highly individualized, particularly when patients are switched from high doses of opioids, given the wide conversion ratios reported in literature.